Light-Based Communication Within Cells Enabled by Hydrogel Implant

The use of light to communicate with cells has been limited by its restricted ability to pass through tissues. Now, researchers at the Wellman Center for Photomedicine at Massachusetts General Hospital (MGH; Boston, USA) published findings of their accomplishment in the October 20, 2013, issue of the journal Nature Photonics.

“Scientists only began investigating light-activated therapy a few years ago, but it is generating huge interest,” said Wellman investigator Seok Hyun Yun, PhD, senior author of the study. “One of the best known examples is use of optogenetics—activation or deactivation of brain cells by illumination with different colors of light to treat brain disorders. But how to deliver light deep within the brain or other tissues has been a common problem. The implant we have developed may help solve this problem.”

The technology is called a light-guiding hydrogel. The implant is made from polymer-based scaffolding capable of supporting living cells and contains cells genetically modified either to perform a specific activity in response to light or to emit light in response to a specific metabolic signal. An optical fiber connects the implant to either an external light source or a light detector.

The investigators first determined the characteristics of the hydrogel scaffolding, including flexibility, transparency, and stability, that would be most appropriate for delivering or detecting a light signal. After figuring out how many cells could be implanted into the hydrogel without significantly reducing its ability to transmit a light signal, they developed and evaluated in mice two different systems, both involving implantation of a 4-cm hydrogel beneath the animal’s skin.

The first system’s implants contained cells genetically engineered to express light-emitting green fluorescent protein (GFP) upon contact with a toxin. After validating in vitro the hydrogels’ response to nanoparticles containing the toxic metal cadmium, the researchers implanted the hydrogels beneath the skin of three groups of mice. One group was then injected with the cadmium nanoparticles, the second received nanoparticles encased in a polymer shell that shielded cells from the toxin, and the third received a control saline injection. The implants only generated a GFP-signal in response to the unshielded nanoparticles, indicating their ability to sense a change, in this case, the presence of a toxin in the cellular environment.

To investigate a possible therapeutic application for the system, the investigators used a hydrogel implant containing cells that respond to blue light by producing glucagon-like peptide-1 (GLP-1), a protein playing an essential role in glucose metabolism. After the implants were placed under the skin of mice with diabetes, the blue light signal was delivered for 12 hours. One day and a half later (48 hours after the implant) the animals that received the light signal had twice the level of GLP-1 in their blood, combined with considerably better results in a glucose tolerance test, than did implanted mice not treated with light.

“This work combines several existing technologies well known in their respective fields, such as drug delivery, genetic engineering, biomaterial science, and photonics, to build a new implant system that enables the delivery of photomedicine deep in the body,” said Dr. Yun, an associate professor of dermatology at Harvard Medical School (Boston, MA, USA) and director of the Harvard Bio-Optics Lab. “This is the first time anyone has shown the ability to talk optically—by means of light—with cells deep within the body, both to sense the presence of a toxin and to deliver a cell-based therapy.”

The researchers added that the next phase of research should examine how altering the shape and structure of the hydrogel can improve the implant’s light-guiding properties, ways to enhance the generation and delivery of a therapeutic protein, how the immune system would react to long-term implantation and ways to deliver or identify the light signal that would not require passing a fiber through the skin.

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